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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

(English title: Physiological Journal)

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2012; 58(2): 89-100


Hypoxic pulmonary hypertension: modern views on pathogenesis and options for rational pharmacological correction

Strielkov IeV, Frantsuzova SB, Khromov OS.

  1. State Institution "Institute of pharmacology and toxicology" of the NAMS of Ukraine
  2. O.O. Bogomoletz Institute of Physiology of the NAS of Ukraine, Ukraine
DOI: https://doi.org/10.15407/fz58.02.089


Abstract

In the article, an analysis of the modern approaches to pharmacological correction of hypoxic pulmonary hyper­tension in conjunction with its development mechanisms has been performed. Promising research trends for the creation of new drugs in this field have also been reviewed. Key words: hypoxic pulmonary hypertension, hypoxia, endothelium, reactive oxygen species, liposomes.

Keywords: hypoxic pulmonary hypertension, hypoxia,endothelium, reactive oxygen species, liposomes.

References

  1. Martyniuk TV, Konosova ID, Chazova IE Modern approaches to drug treatment of pulmonary hypertension . Consilium Med. 2003. N 5. P. 83-86.
  2.  
  3. Solovyov AI, Tishkin SM., Khromov OS, Stefanov OV The contractile function of blood vessels in hypertension of different origins and its correction by phosphatidylcholine liposomes . Fiziol. Zh. 2002. 48. N 6. P 11-17.
  4.  
  5. Strelkov SV., Khromov OS Mechanism of development of hypoxic pulmonary hypertension and its pharmacological correction . Pharmacology and physician. toxicology. 2009. 11. N 4. P 20-25.
  6.  
  7. Khromov OS, Solovyov AI Experimental justification for the use of phosphatidylcholine liposomes in medicine . Pharmacology and physician. toxicology. 2008. N 4-5. p.  88-98.
  8.  
  9. Aaronson P.I., Robertson T.P., Ward J.P. Endothelium-derived mediators and hypoxic pulmonary vasocon­striction . Respir. Physiol. Neurobiol. 2002. 132. P. 107-120. CrossRef.1016/S1569-9048(02)00053-8
  10.  
  11. Adibhatla R.M., Hatcher J.F., Dempsey R.J. Cytidine-52-diphosphocholine (CDP-choline) affects CTP: phosphocholine cytidylyltransferase and lyso-phosphatidylcholine after transient brain ischemia . J. Neurosci. Res. 2004. 76. P. 390-396. CrossRef PubMed
  12.  
  13. Archer S.L., J. Huang, Henry T., Peterson D., Weir E.K. A redox-based O sensor in rat pulmonary vasculature . Circulat. Res. 1993. 73. P. 1100-1112. CrossRef PubMed
  14.  
  15. Archer S., Michelakis E. The mechanism(s) of hypoxic pulmonary vasoconstriction: potassium channels, redox O sensors, and controversies . News Physiol. Sci. 20202. 17. P. 131-137. CrossRef PubMed
  16.  
  17. Baillie J.K, Thompson A.A.R., Irving J.B., Bates M.G.D., Sutherland A.I., MacNee W., Maxwell S.R.J., Webb D.J. Oral antioxidant supplementation does not prevent acute mountain sickness: double blind, randomized placebo-controlled trial . Q.J.M. 2009. 102. P. 341-348. CrossRef PubMed
  18.  
  19. Bhat G.B., Block E.R. Effect of hypoxia on phospho­lipid metabolism in porcine pulmonary artery endothelial cells . Amer. J. Physiol. Lung Cell Mol. Physiol. 1992 262. P. L606-L613. CrossRef PubMed
  20.  
  21. Bigatello L.M., Hurford W.E., Kacmarek R.M., Roberts J.D., Zapol W.M. Prolonged inhalation of ni­tric oxide in patients with severe adult respiratory dis­tress syndrome . Anesthesiology. 1994. 80. P. 761-770. CrossRef PubMed
  22.  
  23. Blythe D., van Heerden P.V. The pulmonary circula­tion and selective pulmonary vasodilators [Elekt­ronnii resurs] . Anaesthetist. 1999.
  24.  
  25. Chandel N.S., Schumacker P.T. Cellular oxygen sens­ing by mitochondria: old questions, new insight . J. Appl. Physiol. 2000. 88. P. 1880-1889. CrossRef PubMed
  26.  
  27. Chang S.W., Stelzner T.J., Weil J.V., Voelkel N.F. Hy­poxia increases plasma glutathione disulfide in rats . Lung. 1989. 167. N 5. P. 269-276. CrossRef PubMed
  28.  
  29. Clutton-Brock J. Two cases of poisoning by contami­nation of nitrous oxide with the higher oxides of nitro­gen during anaesthesia . Brit. J. Anaesth. 1967. 39. P. 388-392. CrossRef PubMed
  30.  
  31. Cohen A. H., Hanson K., Morris K., Fouty B., McMurty I. F., Clarke W., Rodman D.M. Inhibition of cyclic 3'-5'-guanosine monophosphate-specific phosphodiesterase selectively vasodilates the pulmo­nary circulation in chronically hypoxic rats . J. Clin. Invest. 1996. 97. P. 172-179. CrossRef PubMed PubMedCentral
  32.  
  33. Conzen P., Goetz A., Oettinger W., Brendel W. Hy-poxic pulmonary vasoconstriction and endogenous prostaglandin and thromboxane release in anesthetized pigs . Biomed Biochim Acta. 1984. 43. P. S265- S268.
  34.  
  35. Cornfield D.N., Stevens T., McMurtry I.F., Abman S.H., Rodman D.M. Acute hypoxia increases cytosolic calcium in fetal pulmonary artery smooth muscle cells . Amer. J. Physiol. 1993. 265. P. L53-L56. CrossRef PubMed
  36.  
  37. 19. Deleuze P.H., Adnot S., Shiiya N., Thoraval R.F., Eddahibi S., Braquet P. , Chabrier P.E., Loisance D.Y. Endothelin dilates bovine pulmonary circulation and reverses hypoxic pulmonary vasoconstriction . J. Cardiovasc. Pharmacol. 1992. 19. P. 354-360. CrossRef PubMed
  38.  
  39. 20. Du W., Frazier M., McMahon T.J., Eu J.P. Redox Activation of Intracellular Calcium Release Channels (Ryanodine Receptors) in the Sustained Phase of Hypoxia-Induced Pulmonary Vasoconstriction . Chest. 2005. 128. P. 556S-558S. CrossRef.6_suppl.556S PubMed
  40.  
  41. Eddahibi1 S., Hanoun N., Lanfumey L., Lesch K.P., Raffestin B., Hamon M., Adnot S. Attenuated hypoxic pulmonary hypertension in mice lacking the 5-hydroxytryptamine transporter gene . J. Clin. Invest. 2000. 105. P. 1555-1562. CrossRef PubMed PubMedCentral
  42.  
  43. Edwards A. D. The pharmacology of inhaled nitric oxide . Arch. Dis. Child. 1995. 72. P. F127-F130. CrossRef PubMed PubMedCentral
  44.  
  45. Gaine S.P., Hales A., Flavahan N.A. Hypoxic pulmonary endothelial cells release a diffusible contractile factor distinct from endothelin . Amer. J. Physiol. Lung Cell Mol. Physiol. 1998. 274. P. L657-L664. CrossRef PubMed
  46.  
  47. Gonzalez C., Sanz-Alfayate G., Agapito M. T., Gomez-Nino A., Rocher A., Obeso A. Significance of ROS in oxygen sensing in cell systems with sensitivity to physiological hypoxia . Respir. Physiol. Neurobiol. 2002. 132. P. 17-41. CrossRef.1016/S1569-9048(02)00047-2
  48.  
  49. Greenberg B., Kishiyama S. Endothelium-dependent and independent responses to severe hypoxia in rat pulmonary artery . Amer. J. Physiol. Heart Circ. Physiol. 1993. 265. P. H1712-H1720. CrossRef PubMed
  50.  
  51. Gurney A. M.Multiple sites of oxygen sensing and their contributions to hypoxic pulmonary vasocon-striction . Respir. Physiol. Neurobiol. 2002. 132. P. 43-53. CrossRef.1016/S1569-9048(02)00048-4
  52.  
  53. Hampl V. , Tristani-Firouzi M., Nelson D.P., Archer S.L. Chronic infusion of nitric oxide in experimental pulmonary hypertension: pulmonary pressure-flow analysis . European Respiratory Journal. 1996. 9. P. 1475-1481. CrossRef PubMed
  54.  
  55. Hampl V. , Herget J. Role of Nitric Oxide in the Pathogenesis of Chronic Pulmonary Hypertension . Physiol. Rev. 2000. 80. P. 1337-1372. CrossRef PubMed
  56.  
  57. Hasunuma K., Rodman D. M., O'Brien R. F., McMurtry I. F. Endothelin 1 causes pulmonary vasodilation in rats . Amer. J. Physiol. Heart Circ. Physiol. 1990. 259. P. H48-H54. CrossRef PubMed
  58.  
  59. Hill N. Therapeutic options for the treatment of pul­monary hypertension [Elektronnii resurs] . Medscape Pulmonary Medicine. 2005. 9. N 2.
  60.  
  61. Hodyc D., Snorek M., Brtnicky T., Herget J. Superox­ide dismutase mimetic tempol inhibits hypoxic pul­monary vasoconstriction in rats independently of ni­tric oxide production . Exp. Physiol. 2007. 92. P. 945-951. CrossRef PubMed
  62.  
  63. Hoshikawa Y., Ono1 S., Suzuki S., Tanita T., Chida M., Song C, Noda M., Tabata T., Voelkel N.F., Fujimura S. Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia . J. Appl. Physiol. 2001. 90. P. 1299-1306. CrossRef PubMed
  64.  
  65. Joppa P., Petr6jbov6 D., StannGk B., Dorkov6 Z., Tk6Hov6 R. Oxidative stress in patients with COPD and pulmonary hypertension . Wiener Klinische Wochenschrift. 2007. 119. P. 428-434. CrossRef PubMed
  66.  
  67. Kao P.N. Simvastatin treatment of pulmonary hypertension: an observational case series . Chest. 2005. 127. P. 1446-1452. CrossRef.1016/S0012-3692(15)34501-3
  68.  
  69. Kato M., Staub N.C. Response of small pulmonary arteries to unilobar hypoxia and hypercapnia . Circ. Res. 1966. 19. P. 426-440. CrossRef PubMed
  70.  
  71. Knock G.A., Snetkov V.A., Shaifta Y., Connolly M., Drndarski S., Noah A., Pourmahram G.E., Becker, S. Aaronson P.I., Ward J.P. Superoxide constricts rat pulmonary arteries via Rho-kinase-mediated Ca2+ sensitization . Free Radic. Biol. Med. 2009. 46. P. 633-642. CrossRef PubMed PubMedCentral
  72.  
  73. Langleben D., Christman B.W., Barst R.J. Effects of the thromboxane synthetase inhibitor and receptor antagonist terbogrel in patients with primary pulmonary hypertension . Amer. Heart J. 2000. 143. P. E4. CrossRef PubMed
  74.  
  75. Leach R. M., Hill H.S., Snetkov V.A., Ward J.P. Hypoxia, energy state and pulmonary vasomotor tone, Respir . Physiol. Neurobiol. 2002. 132. P. 55-67. CrossRef.1016/S1569-9048(02)00049-6
  76.  
  77. Leach R.M., Hill H.S., Snetkov V.A., Robertson T.P., Ward J.P.T. Divergent roles of glycolysis and the mitochondrial electron transport chain in hypoxic pulmonary vasoconstriction of the rat: identity of the hypoxic sensor . J. Physiol. 2001. 536. P. 211-224. CrossRef PubMed PubMedCentral
  78.  
  79. Leach R.M., Robertson T.P., Twort C.H.C. Hypoxic vasoconstriction in rat pulmonary and mesenteric arteries . Amer. J. Physiol. Lung Cell Mol. Physiol. 1994. 266. P. L223-L231. CrossRef PubMed
  80.  
  81. Littler C.M., Morris K.G., Fagan K.A., McMurtry I.F., Messing R.O., Dempsey E.C. Protein kinase C-epsilon-null mice have decreased hypoxic pulmonary vasoconstriction . Amer. J. Physiol. Heart Circ. Physiol. 2003. 284. P. H1321-H1331. CrossRef PubMed
  82.  
  83. Liu J.Q., Sham J.S., Shimoda L.A., Kuppusamy P., Sylvester J.T. Hypoxic constriction of porcine distal pulmonary arteries: endothelium and endothelin dependence . Amer. J. Physiol. Lung Cell Mol. Physiol. quinone is the electron donor for superoxide formation by complex III of heart mitochondria . Arch. Biochem. Biophys. 1985. 237. P. 408-414.
  84.  
  85. Uzuna Ts., Balbayb Ts., 3omunogluc N. b., Yavuzd Ts., Annakkayab A.N., Gblerd S., Silana C, Erbaee M., Arbak P. Hypobaric-hypoxia-induced pulmonary damage in rats ameliorated by antioxidant erdosteine . Acta Histochemica. 2006. 108. P. 59 68. CrossRef PubMed
  86.  
  87. Vadula M.S., Kleinman J.G., Madden J.A. Effect of hypoxia and norepinephrine on cytoplasmic free Ca2+ in pulmonary and cerebral arterial myocytes . Amer. J. Physiol. 1993. 265. P. L591-L597. CrossRef PubMed
  88.  
  89. Wadsworth R.M. Vasoconstrictor and vasodilator effects of hypoxia . Trends Pharmacol. Sci. 1994. 15. P. 47-53. CrossRef.1016/0165-6147(94)90109-0
  90.  
  91. Ward J.P.T., Snetkov V.A., Aaronson P.I. Calcium, mitochondria and oxygen sensing in the pulmonary circulation . Cell Calcium. 2004. 36. P. 209-220. CrossRef PubMed
  92.  
  93. Ward J.P.T., Knock G.A., Snetkov V.A., Aaronson P.I. Protein kinases in vascular smooth muscle tone role in the pulmonary vasculature and hypoxic pulmonary vasoconstriction . Pharmacol. and Therap. 2004. 104. P. 207-231. CrossRef PubMed
  94.  
  95. Waypa G.B., Marks J.D., Mack M.M., Boriboun C, Mungai P.T., Schumacker P.T. Mitochondrial reactive oxygen species trigger calcium increases during hypoxia in pulmonary arterial myocytes . Circulat. Res. 2002. 91. P. 719-726. CrossRef PubMed
  96.  
  97. Waypa G.B., Chandel N.S., Schumacker P.T. Model for hypoxic pulmonary vasoconstriction involving mitochondrial oxygen sensing . Ibid. 2001. 88. P. 1259-1266. CrossRef PubMed
  98.  
  99. Weir E.K., Hong Z., Porter V.A., Reeve H.L. Redox signaling in oxygen sensing by vessels . Respir. Physiol. Neurobiol. 2002. 132. P. 121-130. CrossRef.1016/S1569-9048(02)00054-X
  100.  
  101. Weir E.K., Archer S.L. The mechanism of acute hypoxic pulmonary vasoconstriction: the tale of two channels . FASEB J. 1995. 9. P. 183-189. CrossRef PubMed
  102.  
  103. Weissmann N., Sommer N., Schermuly R.T., Ghofrani H.A., Seeger W., Grimminger F. Oxygen sensors in hypoxic pulmonary vasoconstriction . Cardiovascular Res. 2006. 71. N 4. P. 620-629. CrossRef PubMed
  104.  
  105. Yuan J. Hypoxic pulmonary vasoconstriction: cellular and molecular mechanisms Springer, 2004. P. 268-269. CrossRef
  106.  
  107. Zhang F., Carson R.C., Zhang H., Gibson G., Thomas H.M. Pulmonary artery smooth muscle cell [Ca2+] and contraction: responses to diphenyleneiodonium i and hypoxia . Amer. J. Physiol. Lung Cell Mol. Physiol. 1997. 273. P. L603-L611. CrossRef PubMed

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